IFNgamma signaling-does it mean JAK-STAT?
The molecular pathways involved in the cellular response to interferon (IFN)gamma have been the focus of much research effort due to their importance in host defense against infection and disease, as well as its potential as a therapeutic agent. The discovery of the JAK-STAT signaling pathway greatly enhanced our understanding of the mechanism of IFNgamma-mediated gene transcription. However, in recent years it has become apparent that other pathways, including MAP kinase, PI3-K, CaMKII and NF-kappaB, either co-operate with or act in parallel to JAK-STAT signaling to regulate the many facets of IFNgamma biology in a gene- and cell type-specific manner. The complex interactions between JAK/STAT and alternate pathways and the impact of these signaling networks on the biological responses to IFNgamma are beginning to be understood. This review summarizes and appraises current advances in our understanding of these complex interactions, their specificity and proposed biological outcomes.
Gough
Daniel J
DJ
Department of Pathology, NYU Cancer Institute, New York University Langone School of Medicine, New York, 10016, USA.
Levy
David E
DE
Johnstone
Ricky W
RW
Clarke
Christopher J
CJ
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D050835:Interferon Regulatory Factors / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D053612:Janus Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D017471:Receptors, Interferon / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000502:physiology; D050799:STAT5 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology; D000096743:Interferon gamma Receptor; D000099232:Proto-Oncogene Protein Spi-1
D022782:CCAAT-Enhancer-Binding Protein-beta; D048049:Extracellular Signal-Regulated MAP Kinases; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D053612:Janus Kinases; D016328:NF-kappa B; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D000096743:Interferon gamma Receptor; D000099232:Proto-Oncogene Protein Spi-1; C083728:MHC class II transactivator protein